دورية أكاديمية
Androgen receptor gene status in plasma DNA associates with worse outcome on enzalutamide or abiraterone for castration-resistant prostate cancer: a multi-institution correlative biomarker study
| العنوان: | Androgen receptor gene status in plasma DNA associates with worse outcome on enzalutamide or abiraterone for castration-resistant prostate cancer: a multi-institution correlative biomarker study |
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| المؤلفون: | Conteduca, V., Wetterskog, D., Sharabiani, M. T. A., Grande, Enrique, Fernández-Pérez, M. P., Jayaram, A., Castellano-Castillo, Daniel, Romanel, A., Lolli, C., Casadio, V., Gurioli, G., Amadori, D., Font, A., Vázquez-Estévez, S., González del Alba, Aránzazu, Mellado, B., Fernández-Calvo, O., Méndez-Vidal, M. J., Climent, M. A., Durán, Ignacio, Gallardo, Eduard, Rodríguez, A., Santander, C., Sáez, María Isabel, Puente, Javier, Gasi Tandefelt, D., Wingate, A., Dearnaley, D., Demichelis, F., de Giorgi, U., González-Billalabeitia, E., Attard, G. |
| المساهمون: | Prostate Cancer UK, Cancer Research UK, Royal Marsden NHS Foundation Trust, The Institute of Cancer Research (UK), European Society for Medical Oncology, Health Research Board (Ireland), Medical Research Council (UK), European Commission, Instituto de Salud Carlos III, Sociedad Española de Oncología Médica, Chris Foundation, Spanish Oncology Genitourinary Group |
| بيانات النشر: | Oxford University Press |
| سنة النشر: | 2017 |
| المجموعة: | Digital.CSIC (Consejo Superior de Investigaciones Científicas / Spanish National Research Council) |
| مصطلحات موضوعية: | Castration-resistant prostate cancer, Androgen receptor, Plasma DNA, Enzalutamide, Abiraterone, Biomarkers |
| الوصف: | [Background] There is an urgent need to identify biomarkers to guide personalized therapy in castration-resistant prostate cancer (CRPC). We aimed to clinically qualify androgen receptor (AR) gene status measurement in plasma DNA using multiplex droplet digital PCR (ddPCR) in pre- and post-chemotherapy CRPC. ; [Methods] We optimized ddPCR assays for AR copy number and mutations and retrospectively analyzed plasma DNA from patients recruited to one of the three biomarker protocols with prospectively collected clinical data. We evaluated associations between plasma AR and overall survival (OS) and progression-free survival (PFS) in 73 chemotherapy-naïve and 98 post-docetaxel CRPC patients treated with enzalutamide or abiraterone (Primary cohort) and 94 chemotherapy-naïve patients treated with enzalutamide (Secondary cohort; PREMIERE trial). ; [Results] In the primary cohort, AR gain was observed in 10 (14%) chemotherapy-naïve and 33 (34%) post-docetaxel patients and associated with worse OS [hazard ratio (HR), 3.98; 95% CI 1.74–9.10; P < 0.001 and HR 3.81; 95% CI 2.28–6.37; P < 0.001, respectively], PFS (HR 2.18; 95% CI 1.08–4.39; P = 0.03, and HR 1.95; 95% CI 1.23–3.11; P = 0.01, respectively) and rate of PSA decline ≥50% [odds ratio (OR), 4.7; 95% CI 1.17–19.17; P = 0.035 and OR, 5.0; 95% CI 1.70–14.91; P = 0.003, respectively]. AR mutations [2105T>A (p.L702H) and 2632A>G (p.T878A)] were observed in eight (11%) post-docetaxel but no chemotherapy-naïve abiraterone-treated patients and were also associated with worse OS (HR 3.26; 95% CI 1.47–not reached; P = 0.004). There was no interaction between AR and docetaxel status (P = 0.83 for OS, P = 0.99 for PFS). In the PREMIERE trial, 11 patients (12%) with AR gain had worse PSA-PFS (sPFS) (HR 4.33; 95% CI 1.94–9.68; P < 0.001), radiographic-PFS (rPFS) (HR 8.06; 95% CI 3.26–19.93; P < 0.001) and OS (HR 11.08; 95% CI 2.16–56.95; P = 0.004). Plasma AR was an independent predictor of outcome on multivariable analyses in both cohorts. ; [Conclusion] ... |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| تدمد: | 0923-7534 1569-8041 |
| العلاقة: | Publisher's version; https://doi.org/10.1093/annonc/mdx155Test; Sí; Annals of Oncology 28(7): 1508-1516 (2017); http://hdl.handle.net/10261/182664Test; http://dx.doi.org/10.13039/501100000771Test; http://dx.doi.org/10.13039/501100004587Test; http://dx.doi.org/10.13039/501100000780Test; http://dx.doi.org/10.13039/100010414Test; http://dx.doi.org/10.13039/501100000265Test; http://dx.doi.org/10.13039/501100000289Test; http://dx.doi.org/10.13039/501100008963Test; http://dx.doi.org/10.13039/501100007075Test; http://dx.doi.org/10.13039/100012139Test |
| DOI: | 10.1093/annonc/mdx155 |
| DOI: | 10.13039/501100000771 |
| DOI: | 10.13039/501100004587 |
| DOI: | 10.13039/501100000780 |
| DOI: | 10.13039/100010414 |
| DOI: | 10.13039/501100000265 |
| DOI: | 10.13039/501100000289 |
| DOI: | 10.13039/501100008963 |
| DOI: | 10.13039/501100007075 |
| DOI: | 10.13039/100012139 |
| الإتاحة: | https://doi.org/10.1093/annonc/mdx155Test https://doi.org/10.13039/501100000771Test https://doi.org/10.13039/501100004587Test https://doi.org/10.13039/501100000780Test https://doi.org/10.13039/100010414Test https://doi.org/10.13039/501100000265Test https://doi.org/10.13039/501100000289Test https://doi.org/10.13039/501100008963Test https://doi.org/10.13039/501100007075Test https://doi.org/10.13039/100012139Test |
| حقوق: | open |
| رقم الانضمام: | edsbas.D7E7F31C |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 09237534 15698041 |
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| DOI: | 10.1093/annonc/mdx155 |